1. cell number (% vehicle control) cisplatin concentration (µM)gefitinib concentration (µM) 10 1 10 2 10 3 cell number expression level (fluorescence intensity) controlEGFR sensitive resistant P-EGFR total EGFR P-AKT total AKT GAPDH S2S2 R2R2 SR P-ERK 1/2 total ERK 1/2 cell number gefitinib concentration (µM) % cells 0.0 0.1 1.0 100 75 50 25 0 100 75 50 25 0 sensitiveresistant Supplementary Fig. S1Box et al. A)B) C) E) D) F)

2. tumour volume (cm 3 ) Supplementary Fig. S2Box et al. A)B) time (days) cell number (% 0 h) time (hours)

3. Supplementary Fig. S3Box et al. gefitinib-treated tumour volume (% day 0) A) 450 400 350 300 250 200 150 100 50 0 B) time (days of therapy) CAL S CAL R CAL S2 CAL R2 gefitinib-treated tumour volume (% vehicle-treated)

4. Supplementary Fig. S4Box et al. A) B) Sensitivity Resistance CAL R only β expression level (arbitrary units) Log 2 ratio of resistant/sensitive expression

5. Supplementary Fig. S5Box et al. A) IL-8 GM-CSF TIMP-1 concentration (pg/ml) * * C) E) * concentration (pg/ml) IL-8 concentration (pg/ml) D) B) F) TIMP-1 concentration (pg/ml) GM-CSF S 2 R 2 con gefitinib S 2 R 2 con gefitinib S 2 R 2 con gefitinib PJ S PJ R con gefitinib PJ S PJ R con gefitinib PJ S PJ R con gefitinib

6. Supplementary Fig. S6Box et al.

7. patient number Supplementary Fig. S7Box et al. IL-8 TIMP-1 concentration (pg/ml) concentration (ng/ml) A) B) patient number

8. Supplementary Fig. S7 (contd.)Box et al. VEGF-A C) concentration (pg/ml) patient number

9. Supplementary Fig. S8Box et al. A) B)